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1.
Heliyon ; 10(3): e25436, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38333872

ABSTRACT

This work experimentally demonstrates the highly-efficient geometric and propagation metasurfaces for vortex beam emissions. These metasurfaces are respectively composed of high-aspect-ratio fin-like and cylindrical gallium nitride (GaN) meta-atoms. Remarkably, the optimized configuration of the fin-like GaN meta-atoms achieves a cross-polarization transmission efficiency of up to 99 %. Similarly, the cylindrical GaN meta-atoms exhibit an average co-polarization transmission efficiency of 97 %. Both metasurfaces, designed for vortex beam emission, exhibit annular intensity converging capabilities at distinct wavelengths in the visible. Notably, the geometric metasurface shows achromatic annular intensity distributions over a continuous wavelength range up to 100 nm, in sharp contrast to the propagation metasurface, which is subject to inherent wavelength dispersion limitations.

2.
Expert Rev Clin Pharmacol ; 17(2): 157-164, 2024.
Article in English | MEDLINE | ID: mdl-38224017

ABSTRACT

BACKGROUND: This study aimed to evaluate the effectiveness and safety of fixed-dose combination (FDC) inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA) in bronchiectasis. RESEARCH DESIGN AND METHODS: A retrospective cohort study analyzed electronic medical records of bronchiectasis patients initiating ICS/LABA FDC or LAMA between 2007 and 2021. All bronchiectasis diagnoses were made by radiologists using high-resolution computed tomography. RESULTS: Of the 1,736 patients, 1,281 took ICS/LABA FDC and 455 LAMA. Among the 694 propensity score matched patients, ICS/LABA FDC had comparable outcomes to LAMA, with HRs of 1.22 (95% CI 0.81-1.83) for hospitalized respiratory infection, 1.06 (95% CI 0.84-1.33) for acute exacerbation, and 1.06 (95% CI 0.66-1.02) for all-cause hospitalization. Beclomethasone/formoterol (BEC/FOR) or budesonide/formoterol (BUD/FOR) led to a lower risk of acute exacerbation compared to fluticasone/salmeterol (FLU/SAL) (BEC/FOR HR 0.59, 95% CI 0.43-0.81; BUD/FOR HR 0.68, 95% CI 0.50-0.93). BEC/FOR resulted in lower risks of hospitalized respiratory infection (HR 0.48, 95% 0.26-0.86) and all-cause hospitalization (HR 0.55, 95% 0.37-0.80) compared to FLU/SAL. CONCLUSION: Our findings provide important evidence on the effectiveness and safety of ICS/LABA FDC compared with LAMA for bronchiectasis. BEC/FOR and BUD/FOR were associated with better outcomes than FLU/SAL.


Subject(s)
Bronchiectasis , Pulmonary Disease, Chronic Obstructive , Humans , Muscarinic Antagonists/adverse effects , Retrospective Studies , Adrenergic beta-2 Receptor Agonists/adverse effects , Pulmonary Disease, Chronic Obstructive/drug therapy , Formoterol Fumarate , Adrenal Cortex Hormones , Fluticasone-Salmeterol Drug Combination/therapeutic use , Bronchiectasis/drug therapy , Administration, Inhalation , Bronchodilator Agents , Drug Therapy, Combination
3.
Int J Mol Sci ; 24(21)2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37958797

ABSTRACT

Idiopathic pulmonary fibrosis has poor clinical outcomes despite antifibrotic treatment. The nucleotide-binding domain leucine-rich repeat-containing receptor, pyrin domain-containing-3 (NLRP3) inflammasome and endothelial-to-mesenchymal transition (EndoMT) were shown to be involved in the pathogenesis of pulmonary fibrosis. However, the detailed mechanism is unknown. Our study aimed to investigate the role of the NLRP3 inflammasome in the regulation of EndoMT in pulmonary fibrosis. The inhibition of the NLRP3 inflammasome via a caspase-1 inhibitor, Ac-YVAD-cmk (YVAD), was intraperitoneally administered to male C57BL/6 mice (8-12 weeks old) one hour before bleomycin intratracheal injection (1.5 U/kg). Immunohistochemical staining, Masson's trichrome staining, enzyme-linked immunosorbent assay, immunofluorescence, and Western blotting were used to assess the activity of the NLRP3 inflammasome and EndoMT in lung samples from mice. Human pulmonary microvascular endothelial cells (HPMECs) were used as a model of EndoMT in vitro with YVAD and bleomycin stimulation. We observed the activation of the NLRP3 inflammasome and EndoMT (decreased vascular endothelial cadherin with increased alpha-smooth muscle actin and vimentin) in the lung samples after bleomycin. However, inhibition of the NLRP3 inflammasome significantly reduces EndoMT via inhibiting focal adhesion kinase (FAK). In vitro studies also confirmed these findings. In conclusion, NLRP3 inflammasome inhibition could reduce lung inflammation and fibrosis via the regulation of EndoMT by the FAK pathway.


Subject(s)
Pulmonary Fibrosis , Male , Humans , Mice , Animals , Pulmonary Fibrosis/metabolism , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Bleomycin/adverse effects , Endothelial Cells/metabolism , Focal Adhesion Protein-Tyrosine Kinases , Mice, Inbred C57BL , Fibrosis
4.
Nanomaterials (Basel) ; 13(19)2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37836321

ABSTRACT

In this work, we have achieved an advancement by integrating wide-angle capacity into vortex beams with an impressive topological charge (TC) of 12. This accomplishment was realized through the meticulous engineering of a propagation-phase-designed metasurface. Comprising gallium nitride (GaN), meta-structures characterized by their high-aspect ratio, this metasurface exhibits an average co-polarization transmission efficiency, reaching a remarkable simulated value of up to 97%. The intricate spiral patterns, along with their respective quantification, have been meticulously investigated through tilt-view scanning electron microscopy (SEM) and were further analyzed through the Mach-Zehnder interferometer. A captivating revelation emerged, a distinctive petal-like interference pattern manifests prior to the metasurface's designed focal distance. The occurrence of this petal-like pattern at a specific z-axis position prompts a deliberate manipulation of the helicity of the spiral branches. This strategic helicity alteration is intrinsically tied to the achievement of a minimized donut diameter at the designed focal length. In regard to the angular capability of the device, the captured images continuously showcase prominent attributes within incident angles spanning up to 30 degrees. However, as incident angles surpass the 30-degree threshold, the measured values diverge from their corresponding theoretical projections, resulting in a progressive reduction in the completeness of the donut-shaped structure.

5.
Opt Lett ; 48(17): 4452-4455, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37656526

ABSTRACT

This Letter describes the design procedure and process optimization of the electrically bifocal metalens. In our design, horizontal and vertical polarization is manipulated by applying a suitable voltage to a twisted nematic liquid crystal (TN-LC) cell. Each nanostructure is designed to be a rectangular prism, making different polarizations of light experience various phase delays, thus causing bi-focus. We selected lithographical methods to fabricate our metalens because of the minimum physical size, which can be as small as 50 nm, and the maximum aspect ratio, which is as high as 15. Furthermore, to increase the tolerance and make the sidewall vertical and smooth, we coated different characteristics of photoresist sensitivity to the upper and lower layers. After the development, the mushroom-type photoresist makes Ni easier to strip while in the lift-off process, thus increasing the quality of the whole metalens. Our experiment shows that the focal lengths and focusing efficiencies corresponding to the two polarizations are similar to the simulation results. The proposed electrically modulated bifocal metalens can be utilized in different applications and combined with other optical components.

6.
Respir Res ; 24(1): 9, 2023 Jan 10.
Article in English | MEDLINE | ID: mdl-36627690

ABSTRACT

We investigated the effects of vegetable glycerin (VG), a main e-cigarette constituent, on endotoxin-induced acute lung injury (ALI). Mice received intratracheal administration of 30% VG in phosphate buffered saline (PBS) vehicle or only PBS (control) for 4 days. On Day 5, mice received an intratracheal instillation of lipopolysaccharide (LPS) (LPS group and VG + LPS group) or PBS (VG group and control group). Lung histopathology, expression of chemokine receptors, and regulatory signaling were analyzed 24 h after the Day 5 treatment. VG significantly increased ALI-associated histopathological and fibrotic changes in both the VG group and LPS-induced ALI mice (VG + LPS group). Immunohistochemistry (IHC) and western blot analyses revealed that VG administration resulted in upregulation of neutrophil markers [lymphocyte antigen 6 complex locus G6D (Ly6G) and myeloperoxidase (MPO)] as well as upregulation of the expression of transforming growth factor-ß (TGF-ß), a central mediator of fibrogenesis, in the lungs of both VG and VG + LPS groups. VG enhanced the expression of adhesion molecules [very late antigen 4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1)] and increased activation of p38 mitogen-activated protein kinase (p38 MAPK) to prompt neutrophil recruitment in the lungs of mice with ALI. Intraperitoneal administration of a p38 inhibitor attenuated these histopathological changes significantly as well as VG-induced upregulation in expression of Ly6G, MPO, VLA-4, VCAM-1, TGF-ß, and collagen-1 in mice with ALI. In conclusion, VG enhances neutrophil chemotaxis and fibrosis and it amplifies the inflammatory response associated with LPS-induced ALI in the lungs via enhancement of p38 MAPK activity.


Subject(s)
Acute Lung Injury , Electronic Nicotine Delivery Systems , Glycerol , Animals , Mice , Acute Lung Injury/metabolism , Fibrosis , Glycerol/adverse effects , Integrin alpha4beta1/metabolism , Lipopolysaccharides/toxicity , Lung/metabolism , Neutrophils/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Transforming Growth Factor beta/metabolism , Vascular Cell Adhesion Molecule-1/metabolism
7.
Biomed J ; 46(3): 100536, 2023 Jun.
Article in English | MEDLINE | ID: mdl-35552020

ABSTRACT

BACKGROUND: Mouth opening/breathing during sleep is common in patients with obstructive sleep apnea (OSA), which is probably associated with more water loss and higher risk for nocturnal ischemic heart attack. This study aimed to evaluate nocturnal changes in hematocrit/hemoglobin levels and estimated plasma volume loss in OSA patients and its relation to their OSA severity and mouth open/breathing. METHODS: Sixty OSA patients and fifteen healthy controls were enrolled and underwent overnight polysomnography. Mouth status was evaluated via an infrared camera and nasal/mouth airflow. Hematocrit and hemoglobin levels in peripheral venous blood were measured before and after sleep to estimate the change of plasma volume. RESULTS: Compared to controls, OSA patients had a greater nocturnal increase in hematocrit (1.35% vs. 1.0%, p = 0.013), hemoglobin (0.50% vs. 0.30%, p = 0.002) and more estimated water loss (5.5% vs 3.7% of plasma volume, p < 0.013). The extent of increase was correlated to apnea-hypopnea index (AHI)_the marker of OSA severity (Spearman's ρ = 0.332, p = 0.004; ρ = 0.367, p = 0.001 for hematocrit, hemoglobin, respectively), which remained significant after serial multivariate adjustment. OSA patients had more sleep time with mouth open (96.7% vs 26.7% of total sleep time, p < 0.001) and time with complete mouth breathing (14.1% vs 2.7%, p < 0.001). The extent of mouth breathing was correlated to AHI (ρ=0.487, p < 0.001), nocturnal increase in hematocrit/hemoglobin levels (ρ = 0.236, p = 0.042; ρ = 0.304, p = 0.008, respectively) and estimated plasma volume loss (ρ = 0.262, p = 0.023). CONCLUSION: OSA patients had a greater increase in hematocrit/hemoglobin levels after sleep, which is probably linked to more water loss and more sleep time with mouth open/breathing.


Subject(s)
Sleep Apnea Syndromes , Sleep Apnea, Obstructive , Humans , Mouth Breathing/complications , Sleep Apnea Syndromes/diagnosis , Sleep Apnea Syndromes/complications , Sleep Apnea, Obstructive/complications , Sleep , Polysomnography
8.
Opt Express ; 31(26): 43089-43099, 2023 Dec 18.
Article in English | MEDLINE | ID: mdl-38178411

ABSTRACT

We experimentally demonstrate a highly efficient metasurface-based optical vortex beam (OVB) composed of high-aspect-ratio gallium nitride (GaN) meta-structures with an exceptional simulated absolute polarization conversion efficiency (APCE) of up to 98%. A flower-like interference pattern emerges at the converging distance of the device with the helicity switching in spiral and dislocation interference patterns beyond this point, as confirmed through meticulous Mach-Zehnder interferometer analysis. The device also performs broadband capabilities across visible wavelengths. Experimentally demonstrated, the annular shape adeptly expands its diameter with increasing incident wavelengths. This phenomenon is rooted in the fascinating anomalous refractive and reflective characteristics inherent to subwavelength-period metasurfaces.

9.
Int J Mol Sci ; 23(15)2022 Jul 25.
Article in English | MEDLINE | ID: mdl-35897764

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease (ILD). Pulmonary fibroblasts play an important role in the development of IPF. Emerging evidence indicates that pulmonary endothelial cells could be the source of pulmonary fibroblasts through endothelial mesenchymal transition (EndoMT), which contributes to pulmonary fibrosis. EndoMT is a complex process in which endothelial cells lose their expression of endothelial markers and give rise to the characteristics of mesenchymal cells, including morphological fibroblast-like change and the expression of mesenchymal markers, which result in cardiac, renal, and dermal fibroses. Furthermore, EndoMT inhibition attenuates pulmonary fibrosis. Herein, we demonstrate that nintedanib, a tyrosine kinase receptor inhibitor, ameliorated murine bleomycin (BLM)-induced pulmonary fibrosis and suppressed the in vivo and in vitro models of EndoMT. We demonstrated that the activity of focal adhesion kinase (FAK), a key EndoMT regulator, increased in murine lung tissues and human pulmonary microvascular endothelial cells after BLM stimulation. Nintedanib treatment inhibited BLM-induced FAK activation and thus suppressed both in vivo and in vitro BLM-induced EndoMT. Importantly, we found that the VEGF/FAK signaling pathway was involved in nintedanib regulating EndoMT. These novel findings help us understand the mechanism and signaling pathway of EndoMT to further develop more efficacious drugs for IPF treatment.


Subject(s)
Bleomycin , Idiopathic Pulmonary Fibrosis , Animals , Endothelial Cells/metabolism , Epithelial-Mesenchymal Transition , Fibrosis , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Humans , Idiopathic Pulmonary Fibrosis/chemically induced , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/metabolism , Indoles , Mice , Protein Kinase Inhibitors/therapeutic use
11.
Allergy Asthma Immunol Res ; 14(3): 314-327, 2022 May.
Article in English | MEDLINE | ID: mdl-35557496

ABSTRACT

PURPOSE: Current clinical guidelines are unclear regarding the association of cardiovascular medication with the risk of acute exacerbation (AE) in patients with asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO). METHODS: We conducted a retrospective cohort study by interrogating the claims database of Taipei Veterans General Hospital. Patients with coexistent fixed airflow limitation and asthma were enrolled as an ACO cohort between 2009 and 2017. Exposure to cardiovascular medications, including angiotensin converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), non-selective beta-blockers, cardioselective beta-blockers, dihydropyridine (DHP) calcium channel blockers (CCBs), and non-DHP CCBs, in 3-month period each served as time-dependent covariates. Patients receiving a cardiovascular medication ≥ 28 cumulative daily doses were defined as respective cardiovascular medication users. Patients were followed up until December 31, 2018. The primary endpoint was severe AE, defined as hospitalization or emergency department visit for either asthma, COPD, or respiratory failure. The secondary outcome was moderate AE. RESULTS: The final study cohort consisted of 582 ACO subjects, with a mean follow-up period of 2.98 years. After adjustment, ARB (hazard ratio [HR], 0.64, 95% confidence interval [CI], 0.44-0.93, P = 0.019), cardioselective beta-blocker (HR, 0.29, 95% CI, 0.11-0.72, P = 0.008) and DHP CCB (HR, 0.66, 95% CI, 0.45-0.97, P = 0.035) therapies were associated with lower risks of severe AE. ARB (HR, 0.42, 95% CI, 0.30-0.62, P < 0.001) and DHP CCB (HR, 0.55, 95% CI, 0.38-0.80, P = 0.002) therapies were associated with lower risks of moderate AE. Cardioselective beta-blockers, ARBs, and DHP CCBs were associated with lower risks of severe AE in frequent exacerbators. ACEI, non-selective beta-blocker, or non-DHP CCB use did not change the risk of severe AE. CONCLUSIONS: ARB, cardioselective beta-blocker, and DHP CCB therapies may lower the risk of AE in patients with ACO.

12.
Sci Adv ; 8(16): eabn5644, 2022 Apr 22.
Article in English | MEDLINE | ID: mdl-35442736

ABSTRACT

Vacuum ultraviolet (VUV) light plays an essential role across science and technology, from molecular spectroscopy to nanolithography and biomedical procedures. Realizing nanoscale devices for VUV light generation and control is critical for next-generation VUV sources and systems, but the scarcity of low-loss VUV materials creates a substantial challenge. We demonstrate a metalens that both generates-by second-harmonic generation-and simultaneously focuses the generated VUV light. The metalens consists of 150-nm-thick zinc oxide (ZnO) nanoresonators that convert 394 nm (~3.15 eV) light into focused 197-nm (~6.29 eV) radiation, producing a spot 1.7 µm in diameter with a 21-fold power density enhancement as compared to the wavefront at the metalens surface. The reported metalens is ultracompact and phase-matching free, allowing substantial streamlining of VUV system design and facilitating more advanced applications. This work provides a useful platform for developing low-loss VUV components and increasing the accessibility of the VUV regime.

13.
Respir Med ; 197: 106833, 2022 06.
Article in English | MEDLINE | ID: mdl-35427844

ABSTRACT

RATIONALE: The association between chronic obstructive pulmonary disease (COPD) and functional gastrointestinal disorders (FGIDs) remains unclear. METHODS: Using Taiwan's National Health Insurance Research Database, we conducted a nationwide population-based study to explore the relationship of COPD and future FGIDs development. The COPD cohort consisted of 4107 patients with COPD between 2000 and 2005. For a comparison cohort, 12,321 age- and gender-matched patients without COPD were randomly selected. The two cohorts were tracked for 5 year and observed for occurrence of FGIDs. The operational definition of COPD in the Korean Health Insurance Review and Assessment Service database was used to validate the results. The validation study confirmed the accuracy of definitions of COPD (83.5% sensitivity). RESULTS: The adjusted hazard ratios (aHR) of FGIDs in patients with COPD was higher (aHR: 1.63; 95% confidence interval (CI): 1.45-1.83; P < .001) than that of the comparison patients. In our secondary analysis in which FGIDs was divided into gastroesophageal reflux disease, irritable bowel syndrome and functional dyspepsia. Patients with COPD also had higher risk for all three subtypes of FGIDs: irritable bowel syndrome (aHR: 1.55; 95% confidence interval (CI): 1.27-1.90; P < .001), gastroesophageal reflux disease (aHR: 2.10; 95% confidence interval (CI): 1.76-2.49; P < .001), and functional dyspepsia (aHR: 1.34; 95% confidence interval (CI): 1.11-1.62; P = .003). The results in validated COPD group were consistent with those in unvalidated COPD group. CONCLUSION: Patients with COPD appeared to be at higher risk for future FGIDs.


Subject(s)
Dyspepsia , Gastroesophageal Reflux , Gastrointestinal Diseases , Irritable Bowel Syndrome , Pulmonary Disease, Chronic Obstructive , Dyspepsia/complications , Dyspepsia/epidemiology , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/epidemiology , Gastrointestinal Diseases/complications , Gastrointestinal Diseases/epidemiology , Humans , Irritable Bowel Syndrome/complications , Irritable Bowel Syndrome/epidemiology , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/epidemiology
14.
Small Methods ; 6(4): e2101228, 2022 04.
Article in English | MEDLINE | ID: mdl-35212186

ABSTRACT

Manipulation and precise delivery of optical energies in the regions of interest within specimens require different strategies. Hence, proper control of input beam parameters is a prerequisite. One of the prominent methods is metasurface optics, capable of crafting properties of light at nanoscales. Here, the generation of an abrupt autofocusing (AAF) beam by a nanophotonic metasurface for biomedical applications is demonstrated. Fluorescence guided laser microprofiling of mouse cardiac samples is experimentally investigated, using the AAF beam to deliver optical energy selectively to specific locations. In addition, photocoagulation of ex vivo swine skin tissue is performed and observed through optical coherence tomography. The results show great potentials for integrating metasurface optics to realize miniature laser surgery instruments for wide applications in biomedicine.


Subject(s)
Lasers , Optics and Photonics , Animals , Mice , Swine
15.
J Chin Med Assoc ; 85(2): 167-174, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34974511

ABSTRACT

BACKGROUND: Patients with traumatic spinal cord injury (SCI) at C3-C5 have a wide range of tracheostomy rates (27%-75%), and the influencing factors for tracheostomy remain unclear. We conducted a retrospective case-control study to identify the influencing factors for tracheostomy in this subset of patient population. METHODS: A total of 101 acute traumatic C3-C5 SCI patients with acute respiratory failure requiring translaryngeal intubation and invasive mechanical ventilation (IMV) for more than 48 hours were identified and divided into the no tracheostomy (No-TCO, n = 59) and tracheostomy group (TCO, n = 42) groups. Clinical data were retrospectively reviewed and analyzed. RESULTS: Compared with the No-TCO patients, the TCO patients had a higher proportion of C3 level injury, lower Glasgow Coma Scale (GCS), and lower blood hemoglobin levels at admission. During the first weaning attempt, the TCO patients had lower levels of maximal inspiratory pressure, maximal expiratory pressure, and minute ventilation but had a higher level of rapid shallow breathing index (RSBI). The TCO patients had longer durations of IMV, ICU stay, and hospitalization compared with the No-TCO patients. Moreover, due to prolonged IMV, the TCO patients had a higher incidence of complications, including ventilator-associated pneumonia, bacteremia, urinary tract infection, and acute kidney injury compared with the No-TCO patients. Multivariate logistic regression analysis revealed that low GCS at admission and high initial RSBI were independent risk factors for tracheostomy. Importantly, a combination of these two influencing factors synergistically increased the odds ratio for tracheostomy. CONCLUSION: Low GCS at admission and high initial RSBI are two independent influencing factors that synergistically impact tracheostomy in our patients. These findings are helpful for making the decision of performing tracheostomy in this subset of patient population.


Subject(s)
Respiratory Distress Syndrome , Spinal Cord Injuries/physiopathology , Tracheostomy , Adult , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , ROC Curve , Retrospective Studies , Taiwan
16.
Int J Mol Sci ; 22(18)2021 Sep 13.
Article in English | MEDLINE | ID: mdl-34576061

ABSTRACT

The role of nintedanib, a multiple tyrosine kinase inhibitor, in the treatment of sepsis-induced acute lung injury (ALI) remains unclear. Lipopolysaccharide (LPS), also known as endotoxin, has been used to induce ALI. The goal of this study was to assess the effect of nintedanib in attenuating the histopathological changes of LPS-induced ALI. Nintedanib was administered via oral gavage to male C57BL/6 mice 24 h and 10 min before intratracheal endotoxin instillation. Lung histopathological characteristics, adhesion molecule expression, and the regulatory signaling pathways of neutrophil chemotaxis were analyzed after 24 h. We found that nintedanib significantly reduced histopathological changes and neutrophil recruitment in LPS-induced ALI. The number of neutrophils in bronchoalveolar lavage fluid (BALF) was reduced in nintedanib-treated relative to untreated mice with ALI. Nintedanib mediated the downregulation of the chemotactic response to LPS by reducing the expression of adhesion molecules and the phosphorylated p38:total p38 mitogen-activated protein kinase (MAPK) ratio in the lungs of mice with ALI. Nintedanib also reduced the expression of lymphocyte antigen 6 complex locus G6D (Ly6G) and very late antigen 4 (VLA-4) in BALF neutrophils and mediated the downregulation of chemokine (C-X-C motif) receptor 2 (CXCR2) and upregulation of G protein-coupled receptor kinase 2 (GRK2) activity in peripheral blood neutrophils in mice with LPS-induced ALI. Nintedanib improved the histopathological changes of LPS-induced ALI by reducing neutrophil chemotaxis. These effects were mediated by the inhibition of adhesion molecules via the activation of GRK2 and the inhibition of p38 MAPK and CXCR2.


Subject(s)
Acute Lung Injury/drug therapy , G-Protein-Coupled Receptor Kinase 2/genetics , Indoles/pharmacology , Receptors, Interleukin-8B/genetics , p38 Mitogen-Activated Protein Kinases/genetics , Acute Lung Injury/chemically induced , Acute Lung Injury/genetics , Animals , Antigens, Ly/genetics , Bronchoalveolar Lavage Fluid , Disease Models, Animal , Endotoxins/toxicity , Integrin alpha4beta1/genetics , Lipopolysaccharides/toxicity , Neutrophils/metabolism , Neutrophils/pathology , Sepsis/chemically induced , Sepsis/complications , Sepsis/drug therapy , Sepsis/pathology
17.
Nat Sci Sleep ; 13: 1631-1640, 2021.
Article in English | MEDLINE | ID: mdl-34584477

ABSTRACT

PURPOSE: Asthma, which is caused by inflammation of the airways, affects the sensitivity of nerve endings. Narcolepsy is a chronic sleep disorder that may be caused by autoimmunity. Recent studies have reported a positive association between narcolepsy and asthma. We aimed to examine the association between asthma and narcolepsy and determine the effects of therapeutic corticosteroid or bronchodilator use. MATERIALS AND METHODS: We conducted a nationwide population-based, nested case-control study using Taiwan's National Health Insurance Research Database (NHIRD) between 2000 and 2013. Subjects with narcolepsy (ICD-9-CM code 347) were enrolled, with 1:3 estimated propensity score-matched controls based on sex, age, and index year. The association between narcolepsy and asthma was assessed using multiple logistic regression analyses. The covariates included sex, age, monthly insurance premiums, geographical area of residence, urbanization level of residence, level of care, and presence of diseases related to immune response and central nervous system. The effects of corticosteroid and bronchodilator use were also analyzed. RESULTS: Overall, 2008 subjects were identified from the NHIRD (502 patients with narcolepsy and 1506 controls). The participants with narcolepsy had almost three times the level of previous asthma diagnosis than controls. Compared to those without asthma, patients with asthma had an adjusted odds ratio (OR) of 3.181 for narcolepsy comorbidity (95% confidence interval [CI]: 2.048-4.941, p<0.001). The use of inhaled corticosteroids was associated with a lower risk of narcolepsy comorbidity, with an adjusted OR of 0.465 (95% CI, 0.250-0.634; p<0.001), in patients with asthma when compared to those without treatment. CONCLUSION: This study demonstrated a significantly higher level of previous asthma diagnosis in patients with narcolepsy. The use of inhaled corticosteroids was associated with a lower risk of narcolepsy comorbidity in asthma patients, compared to those without treatment.

18.
Sci Rep ; 11(1): 14541, 2021 Jul 15.
Article in English | MEDLINE | ID: mdl-34267286

ABSTRACT

The growth of wide-bandgap materials on patterned substrates has revolutionized the means with which we can improve the light output power of gallium nitride (GaN) light-emitting diodes (LEDs). Conventional patterned structure inspection usually relies on an expensive vacuum-system-required scanning electron microscope (SEM) or optical microscope (OM) with bulky objectives. On the other hand, ultra-thin metasurfaces have been widely used in widespread applications, especially for converging lenses. In this study, we propose newly developed, highly efficient hexagon-resonated elements (HREs) combined with gingerly selected subwavelength periods of the elements for the construction of polarization-insensitive metalenses of high performance. Also, the well-developed fabrication techniques have been employed to realize the high-aspect-ratio metalenses working at three distinct wavelengths of 405, 532, and 633 nm with respective diffraction-limited focusing efficiencies of 93%, 86%, and 92%. The 1951 United States Air Force (USAF) test chart has been chosen to characterize the imaging capability. All of the images formed by the 405-nm-designed metalens show exceptional clear line features, and the smallest resolvable features are lines with widths of 870 nm. To perform the inspection capacity for patterned substrates, for the proof of concept, a commercially available patterned sapphire substrate (PSS) for the growth of the GaN LEDs has been opted and carefully examined by the high-resolution SEM system. With the appropriately chosen metalenses at the desired wavelength, the summits of structures in the PSS can be clearly observed in the images. The PSS imaging qualities taken by the ultra-thin and light-weight metalenses with a numerical aperture (NA) of 0.3 are comparable to those seen by an objective with the NA of 0.4. This work can pioneer semiconductor manufacturing to choose the polarization-insensitive GaN metalenses to inspect the patterned structures instead of using the SEM or the bulky and heavy conventional objectives.

19.
Int J Mol Sci ; 22(11)2021 May 24.
Article in English | MEDLINE | ID: mdl-34074039

ABSTRACT

The conditioned medium of induced pluripotent stem cells (iPSC-CM) can attenuate neutrophil recruitment and endothelial leakage of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Therefore, we investigated the mechanisms by which iPSC-CM regulate the interaction between neutrophils and the endothelium in ALI. Murine iPSCs (miPSCs) were delivered intravenously to male C57BL/6 mice (8-12 weeks old) 4 h after intratracheal LPS injection. A miPSC-derived conditioned medium (miPSC-CM) was delivered intravenously to mice after intratracheal LPS injection. DMSO-induced HL-60 cells (D-HL-60, neutrophil-like cells) and human umbilical vein endothelial cells (HUVECs) were used as in vitro models to assess the interaction of neutrophils and endothelial cells. miPSC-CM diminished the histopathological changes in the lungs and the neutrophil count in bronchoalveolar lavage fluids of ALI mice. miPSC-CM attenuated the expression of adhesion molecules in the lungs of ALI mice. Human iPSC conditioned medium (hiPSC-CM) reduced the expression of adhesion molecules in a HUVEC and D-HL-60 co-culture after LPS stimulation, which decreased the transendothelial migration (TEM) of D-HL-60. A human angiogenesis factors protein array revealed that leukemia inhibitory factor (LIF) was not detected in the absence of D-HL-60 and hiPSC-CM groups. hiPSC-CM significantly promoted the production of endogenous LIF in in vitro models. Administration of an anti-LIF antibody not only reversed the effect of iPSC-CM in ALI mice, but also blocked the effect of iPSC-CM on neutrophils TEM in in vitro models. However, a controlled IgG had no such effect. Our study demonstrated that iPSC-CM promoted endogenous LIF to inhibit neutrophils TEM and attenuate the severity of sepsis-induced ALI.


Subject(s)
Acute Lung Injury/metabolism , Culture Media, Conditioned/pharmacology , Induced Pluripotent Stem Cells/metabolism , Leukemia Inhibitory Factor/metabolism , Acute Lung Injury/chemically induced , Acute Lung Injury/pathology , Animals , Cell Movement/drug effects , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Endotoxins/toxicity , Human Umbilical Vein Endothelial Cells , Humans , Male , Mice , Mice, Inbred C57BL , Neutrophils/drug effects , Neutrophils/metabolism
20.
Sci Rep ; 11(1): 6500, 2021 Mar 22.
Article in English | MEDLINE | ID: mdl-33753823

ABSTRACT

Metalens is one of the most promising applications for the development of metasurfaces. A wide variety of materials have been applied to metalenses working at certain spectral bands in order to meet the requirements of high efficiency and low-cost fabrication. Among these materials, wide-bandgap gallium nitride (GaN) is one of the most promising materials considering its advantages especially in semiconductor manufacturing. In this work, GaN has been utilized to fabricate the high-performance metalenses operating at visible wavelengths of 405, 532, and 633 nm with efficiencies up to 79%, 84%, and 89%, respectively. The homemade 1951 United State Air Force (UASF) resolution test chart has also been fabricated in order to provide resolvable lines with widths as small as 870 nm. As shown in the experimental results for imaging, the metalens designed at 405 nm can provide extremely high resolution to clearly resolve the smallest lines with the nano-sized widths in the homemade resolution test chart. These extraordinary experimental results come from our successful development in design and fabrication for the metalenses composed of high-aspect-ratio GaN nanoposts with nearly vertical sidewalls.

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